The proposed research is designed to investigate the neural mechanisms of operant conditioning. The specific aim is to attempt to define the functional unit in the brain for positive reinforcement. Does the individual brain cell have the capacity for operant conditioning, or must some larger organizational unit -- perhaps the substrate of the whole response itself -- be identified? And even if the operant conditioning of single units can be demonstrated does such a cellular process contribute significantly to behavioral operant conditioning? These questions will be evaluated primarily by use of two recently developed methods for the localization of chemical reinforcement effects in the brain. In the first method (brain self-administration), a behavioral response will be reinforced by direct injections of transmitters or drugs into specific brain regions. In the second method ("neuronal operant conditioning"), the activity of neurons in brain slices form the same regions will be reinforced by cellular application of the transmitters and drugs. Appropriate pharmacological antagonist will be used to identify the brain receptors that may be associated with reinforcing effects in the two tests. The experimental plan proposes concurrent use of both operant conditioning methods in an attempt to correlate the reinforcing effects of transmitter and drugs at the behavioral and cellular levels. It is widely believed that the pathophysiology of certain mental disorders -- such as schizophrenia, mania, and depression -- involves dysfunction of behavioral reinforcement mechanisms. Elucidation of the biology underlying these mechanisms may open new approaches to the treatment of mental disease.